Veterinary feedstuffs

ABSTRACT

Imines of 2-formylquinoxaline-3-carboxylic acid-1,4-dioxides and their salts are obtained through treatment of the lactone or a salt of 2-dihydroxymethylquinoxaline-N,N-dioxide-3-carboxylic acid with a reactant bearing a free primary amino group. Veterinary feedstuffs are produced by combining a nutritious material with an imine as above described.

This is a divisional of our copending application Ser. No. 399,098 filedSept. 20, 1974; which is a divisional of our application Ser. No.323,953 filed Jan. 15, 1973, now U.S. Pat. No. 3,856,957 issued Dec. 24,1974; which itself is a divisional of our application Ser. No. 130,007,filed Mar. 31, 1971, now U.S. Pat. No. 3,819,616 issued June 25, 1974.

The present invention relates to new imines of2-formyl-quinoxaline-3-carboxylic acid-1,4-dioxides and their salts, toprocesses for their preparation, to the use of the new compounds asmedicaments in human medicine and veterinary medicine, to their use asfeedstuff additives, especially in raising young animals or fatstock,and to compositions adapted to this use.

The new imines and salts have the general formula: ##SPC1##

Wherein

Y is hydrogen, an alkali metal cation or the cation R⁵ --NH₃ ^(+;) and

Each of R and R⁵ is identical to or different from the other and isselected from the group consisting of

A. alkyl, substituted alkyl or cycloalkyl;

B. ##STR1##in which each of R¹ and R² when taken independently isidentical to or different from the other, and is selected from the groupconsisting of hydrogen, alkyl or substituted alkyl, or when R¹ and R²are taken together with the nitrogen atom to which they are attached a5- to 7-membered heterocyclic ring optionally containing as a ringmember oxygen, sulphur, SO₂ or N-alkyl;

C. ##STR2## in which X is O, S or NH and, R¹ and R² are as abovedefined; D. ##STR3## in which R³ is alkyl or substituted alkyl; E.##STR4## in which R⁴ is phenyl, pyridyl or norbornyl, and X is asdefined above;

F. ##STR5## in which R¹, R² and X are as defined above; or G. ##SPC2##

A preferred group of the imines and salts of the invention are those ofthe above general formula (1), in which:

Y has the meanings given above;

Each of R and R⁵ is identical to or different from the other and isselected from the group consisting of

A. alkyl or hydroxyalkyl of from 1 to 4 carbon atoms or a 6-membered or7-membered monocyclo- or bi-cycloalkyl group;

B. ##STR6## in which each of R¹ and R² when taken independently isidentical to or different from the other and is selected from the groupconsisting of hydrogen, alkyl or hydroxyalkyl of from 1 to 4 carbonatoms, or when R¹ and R² are taken together with the nitrogen atom towhich they are attached, a 6-membered heterocylic ring optionallycontaining as a ring member oxygen or SO₂ ;

c. ##STR7## in which X is O, S or NH, and R¹ and R² are as hereindefined; d. ##STR8## in which R³ is alkyl or hydroxyalkyl of from 1 to 4carbon atoms; and e. ##STR9## in which R⁴ is phenyl, pyridyl ornorbornyl, and X is as herein defined.

Alphatic groups embraced by R and R⁵ include straight-chain or branchedalkyl groups of from 1 to 6, preferably 1 to 4, carbon atoms.Cycloaliphatic radicals contain from 3 to 7, preferably 5 to 7, carbonatoms and include both monocyclic and bicyclic ring systems.

These aliphatic or cycloaliphatic groups can be optionally substituted,for example, by hydroxy, alkoxy, or acyloxy, the alkoxy and acyloxygroups containing 1 to 4, preferably 1 or 2, carbon atoms. The hydroxygroup is the preferred substituent. Typical aliphatic and cycloaliphaticgroups thus include methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, tert.-butyl, n-pentyl, isopentyl, hexyl, 2-hydroxyethyl,cyclopropyl, cyclopentyl, cyclohexyl, bicyclo-(2,2,1)-heptyl(norbornyl), and the like.

The substituents R¹ and R² are hydrogen or alkyl of from 1 to 4,preferably 1 or 2, carbon atoms. These alkyl groups can be optionallysubstituted with hydroxy, alkoxy or acyloxy, alkoxy and acyloxy groupscontaining 1 to 4, preferably 1 or 2, carbon atoms. Thus included areethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert.-butyl, as wellas the corresponding groups substituted by hydroxy.

R¹ and R² when taken together with the nitrogen atom to which they areattached, can also form a heterocyclic ring, preferably containing 6ring members, and preferably with an oxygen atom, a sulphur atom, anN-alkyl group containing 1 to 4, preferably 1 or 2, carbon atoms, or theSO₂ group, as a ring member in the p-position relative to the nitrogenatom to which R¹ and R² are attached.

R³ is an alkyl of from 1 to 4, preferably 1 or 2, carbon atoms which mayalso be optionally substituted by hydroxy, alkoxy, acyloxy, alkoxy andacyloxy containing 1 to 4, preferably 1 or 2, carbon atoms. The hydroxygroup is a particularly preferred substituent. R³ thus embraces suchgroups as methyl, ethyl, 2-hydroxyethyl and the like.

The alkali metal cation Y is, for example, that of sodium or potassium,preferably that of sodium.

R⁴ is phenyl, pyridyl or norborn-2-yl. When R⁴ is pyridyl, it can bebonded in the 2-, 3- or 4-position relative to the pyridyl nitrogenatom.

The above class of imines are obtained according to the process of thepresent invention by treatment of1-oxo-3-hydroxy-1,3-dihydro-furo-(3,4-b)-quinoxaline-4,9-dioxide, whichhas the formula: ##SPC3##

or a salt thereof of the formula ##SPC4##

with an amine of the general formula H₂ N--R, in which R is aspreviously defined, M is an alkali metal or alkaline earth metal cationand x is 1 or 2.

The salts of the formula can be obtained from the lactone of formulathrough treatment with alkali metal or alkaline earth metal hydrogencarbonates.

M is preferably the cation of sodium, potassium or most preferablycalcium.

Both inorganic and organic polar solvents can be used as diluents forthe reaction according to the invention, such as for example water,lower aliphatic alcohols of 1 to 4 carbon atoms, lower aliphaticnitriles such as acetonitrile, tetrahydrofurane, dioxane,dimethoxyethane, pyridine, dimethylformamide and the like.

The reaction according to the invention is carried out at a temperatureof about 0° to about 50° C, preferably 20° to about 35° C.

In practice, the lactone or lactone salts are dissolved or suspended inthe diluent, and this solution or suspension is then treated with anappropriate quantity of the amine. The formation of the imine or of theimine salt takes place in a weakly exothermic reaction and the finalproduct is then isolated through conventional methods.

The imine salts (1) can also be prepared by the reaction of the freeacids with amines.

The salts may be obtained in a subsequent step by conventionaltechniques or directly in the reaction of the lactone with the amine. Ifabout 2 mols of the amine per mol of lactone are employed, the productwill be in the form of that amine salt. If an alkali metal salt oralkaline earth metal salt of the lactone is employed, or if it isdesired to obtain the free acid from the lactone, only about 1 mol ofthe amine per mol of the lactone or salt is required.

The course of the process according to the invention can thus beillustrated by the following equations:

The following examples will serve to further typify the nature of thisinvention without being a limitation on the scope thereof.

EXAMPLE 1

23.4 g (0.1 mol) of1-oxo-3-hydroxy-1,3-dihydrofuro-(3,4-b)-quinoxaline-4,9-dioxide aresuspended in 60 ml of water and 20 G (0.2 mol) of 60% strength aqueousisopropylamine solution are added. The temperature is kept below 30° Cby slight cooling. After a few minutes, a clear solution is produced.Evaporation in vacuo yields 45 g of the compound of the formula ##SPC5##

in the form of yellow crystals, which after recrystallisation fromisopropanol melt at 123°-25° C, with decomposition.

Analysis: C₁₆ H₂₂ N₄ O₄ (molecular weight 334). Calculated: C, 57.5%; H,6.6%; N 16.8%. Found: C, 57.1%; H, 5.8%; N 16.8%.

EXAMPLE 2

27.4 g (0.1 mol) of the Na salt of 2-(di-hydroxymethyl)-3-carboxylicacid-quinoxaline-di-N-oxide are dissolved in 100 ml of water and 7.3 g(0.1 mol) of tert.-butylamine are added. The temperature is kept at 25°C by cooling. After 1 hour, the solution is evaporated in vacuo and 32 gof the compound of the formula ##SPC6##

are obtained in the form of yellow crystals which afterrecrystallisation from acetonitrile/water melt at 228° C, withdecomposition.

Analysis: C₁₄ H₁₄ N₃ NaO₄ (molecular weight 311). Calculated: C, 54.0%;H, 4.5%; N, 13.5%; Na, 7.4%. Found: C, 53.7%; H, 4.9%; N, 13.5%; Na,6.9%.

The 1-oxo-3-hydroxy-1,3-dihydro-furo(3,4-b)-quinoxaline-4,9-dioxide ofthe formula (I) required as the starting compound can be obtained asfollows:

30.7 g (0.1 mol) of2-bismethoxy-methyl-3-dimethylaminocarbonyl-quinoxaline-1,4-di-N-oxideare introduced into 100 ml of 10% strength aqueous hydrochloric acid. Aclear solution results, and after a short time the compound according tothe invention separates out in the form of a yellow precipitate, whichis filtered off after 6 hours. 17 g (72.6% of theory) of1-oxo-3-hydroxy-1,3-dihydro-furo-(3,4-b)-quinoxaline-4,9-dioxide arethus obtained in the form of yellow crystals.

The compound is purified by dissolving it in sodium bicarbonatesolution, filtering and acidifying the filtrate. The purified compoundmelts at 156° - 159° C, whilst foaming.

Analysis: C₁₀ H₆ N₂ O₅ (235). Calculated: C, 51.3%; H, 2.6%; N, 12.0%.Found: C, 52.0%; H, 2.8%; N, 12.6%.

The alkali metal salts or alkaline earth metal salts of1-oxo-3-hydroxy-1,3-dihydro-furo-(3,4-b)quinoxaline-4,9-dioxide can bemanufactured as follows:

The lactone (9) is suspended in water and approximately thestoichiometrically required amount of the alkali metal hydrogencarbonate or alkaline earth metal hydrogen carbonate is added at roomtemperature. The salt of the lactone (10), thus produced, precipitates,after evaporation of the solution if necessary, and can be isolated inthe usual manner.

The following are obtained analogously to Examples 1 and 2: ##SPC7####SPC8## ##SPC9## ##SPC10## ##SPC11## ##SPC12##

As has already been mentioned, the new compounds of the inventionsurprisingly show an excellent chemotherapeutic activity. Theirchemotherapeutic action was examined both in animal experiments (oraland subcutaneous administration) with acute bacterial infections, and invitro. In both cases the compounds show a very good antibacterialaction, and the range of action encompasses both Gram-negative andGram-positive bacteria. The chemotherapeutic activity of the compoundsaccording to the invention permits their use in human medicine and inveterinary medicine. Furthermore, the compounds can be employed asfeedstuff additives, especially in raising young animals or fatstock.The good 1, vitro and in vivo activity of the compounds according to theinvention can be seen from Tables 1, 2 and 3 below.

The minimum inhibitory concentrations in vitro for some of the newcompounds shown in Table 1 (MIC) were determined by the plate test in anagar medium of the following composition:

    ______________________________________                                        proteose peptone   10.0 g    per liter                                        veal extract (solids)                                                                            10.0 g    "                                                dextrose           2.0 g     "                                                sodium chloride    3.0 g     "                                                disodium phosphate 2.0 g     "                                                sodium acetate     1.0 g     "                                                adenine sulphate   0.01 g    "                                                guanine hydrochloride                                                                            0.01 g    "                                                uracil             0.01 g    "                                                xanthin            0.01 g    "                                                neutral agar       12.0 g    "                                                ______________________________________                                    

5.10 × 10³ germs were inoculated per plate. Readings were taken after 24and 48 hours, and the incubation temperature was about 37° C.

                  Table 1                                                         ______________________________________                                        MIC in γ/ml of medium                                                               Compound of                                                                              Compound of                                                                              Compound of                                 Bacterium   Example 10 Example 12 Example 13                                  ______________________________________                                        Escherichia                                                                   coli A 261                        20                                          Escherichia                                                                   coli C 165                        50                                          Proteus vulgaris                                                              species                150        10                                          Pseudomonas                                                                   aeruginosa                                                                    Bonn        100                   100                                         Pseudomonas                                                                   aeruginosa                                                                    Walter                            100                                         Klebsiella                                                                    pneumonia 63                      100                                         Kletosiella                                                                   pneumonia 8085                    20                                          Staphylococcus                                                                aureus 133                        10                                          Streptococcus                                                                 pyogenes W                        100                                         ______________________________________                                    

Table 2

Minimum inhibitory concentration (MIC) in γ/ml of medium, measured bythe series dilution test (complete medium), incubation temperature: 37°C, determination of the MIC after 18, 24 and 48 hours.

    ______________________________________                                                                   Compound of                                        Bacterium                  Example 13                                         ______________________________________                                        Streptococcus faecalis ATCC 9700                                                                          50                                                Streptococcus faecalis ATCC 8564                                                                         100                                                Streptococcus faecalis ATCC 8580                                                                          50                                                Streptococcus faecalis ATCC 8698                                                                         100                                                Streptococcus faecalis ATCC 8699                                                                         100                                                Streptococcus faecalis ATCC 8711                                                                          50                                                Streptococcus faecalis ATCC B. H.                                                                        100                                                Streptococcus faecalis ATCC Blaschke                                                                      6-25                                              Streptococcus faecalis ATCC 13                                                                            25                                                Streptococcus faecalis ATCC species                                                                      100                                                Streptococcus faecalis ATCC liquef.                                                                       50                                                Streptococcus faecalis ATCC durans                                                                        25                                                Escherichia coli C 165      50-100                                            Escherichia coli 2         25- 50                                             Escherichia coli 55 B 5    3-6                                                Escherichia coli 14        12- 25                                             Escherichia coli A 261     25-50                                              Escherichia coli 183/58     6-12                                              Proteus mirabilis G         12                                                Proteus mirabilis 2935      12                                                Proteus vulgaris 3400       50                                                Proteus vulgaris 1017       17                                                Pseudomonas aeruginosa W   400                                                Pseudomonas aeruginosa M    25                                                Pseudomonas aeruginosa B    25                                                Klebsiella ATCC 10031      1-2                                                Klebsiella K 10             50                                                Klebsiella 63               50                                                Salmonella paratyphii BB II                                                                               12                                                Corynebacterium diphteriae gravis                                                                         5-10                                              Staphylococcus aureus 133  1                                                  Staphylococcus aureus 7705  12                                                Staphylococcus aureus BRL   12                                                Neisseria catharalis N 1/41                                                                              6                                                  Mycoplasma gallisepticum   6                                                  Mycoplasma gallisepticum*) 6                                                  Mycoplasma granularum*)    3                                                  Mycobacterium tuberculosis H 37 RV                                                                        40                                                ______________________________________                                          *)measured in a PPLO medium                                             

For the compound of Example 3, the following minimal inhibitoryconcentrations (MIC) (γ/ml of nutrient medium) were measured by theseries dilution test (PPLO medium), incubation temperature 37° C,determination after 18, 24 and 48 hours.

    ______________________________________                                               Bacterium         MIC                                                  ______________________________________                                        Mycoplasma gallisepticum 100                                                  Mycoplasma granularum     25                                                  Mycoplasma bovirhinis    200                                                  ______________________________________                                    

In animal experiments on mice, the effective 100% dose (ED₁₀₀) in mg/Kgwas determined for certain compounds of the invention afterintraperitoneal infection and subcutaneous (s.c.) or oral (p.o.)administration of the preparation.

                                      Table 3                                     __________________________________________________________________________           Compound of                                                                           Compound of                                                                           Compound of                                                                           Compound of                                           Example 3                                                                             Example 8                                                                             Example 13                                                                            Example 14                                     Bacterium                                                                            s.c.                                                                              p.c.                                                                              s.c.                                                                              p.c.                                                                              s.c.                                                                              p.c.                                                                              s.c.                                                                              p.c.                                       __________________________________________________________________________    Escherichia                                                                          50  100 50  100 25  25  50  100                                        coli C 165                                                                    Staphylococ-                                                                         --  --  --  --  25  50  --  --                                         cus aureus                                                                    133                                                                           __________________________________________________________________________

In general, it has proved advantageous, in acute general infections, toadminister amounts of about 5 mg to about 200 mg per kilogram,preferably about 25 to about 50 mg per kilogram of body weight per day,to achieve effective results. Nevertheless it can at times be necessaryto deviate from the amounts mentioned, in particular depending on thebody weight of the test animal or patient or on the nature of the methodof administration, but also because of the type of animal and itsindividual behaviour towards the medicament, or because of the nature ofthe formulation of the latter, and the point in time or interval atwhich administration takes place. Thus it can, in some cases, suffice touse less than the abovementioned minimum amount, whilst in other casesthe upper limit mentioned must be exceeded. In the case of theadministration of larger amounts it can be advisable to divide theseinto several individual doses over the course of the day. The same rangeof dosages is envisaged for administration in human medicine. The othercomments made above also apply in a general sense.

Accordingly, the present invention provides a pharmaceutical compositioncontaining as an active ingredient at least one of the new compounds ofthe general formula (1) given above in admixture with a pharmaceuticallyacceptable solid or liquid diluent or carrier as hereinafter defined.

In the present specification the expression "pharmaceutically acceptablediluent or carrier" means a non-toxic substance that when mixed with theactive ingredient or ingredients renders it suitable for administration.The expression preferably excludes water and low-molecular weightorganic solvents commonly used in chemical synthesis, except in thepresence of other pharmaceutically necessary ingredients such as saltsin correct quantities to render the composition isotonic, buffers,surfactants, colouring and flavouring agents, and preservatives.Examples of suitable liquid diluents and carriers are vegetable oils,glycerol, propylene glycol, polyols, buffered aqueous solutions,isotonic saline aqueous solutions, syrups and lotion bases. Examples ofsuitable solid diluents and carriers are starches, cellulose and itsderivatives, sugars, stearates and stearic acid, talc, and ointmentbases. Examples of pharmaceutical compositions according to theinvention are ointments, pastes, creams, sprays, lotions, aqueous andnon-aqueous suspensions, emulsions, and solutions (includingparenterally injectable solutions), elixirs and syrups, and granulatesand powders either free-flowing or compressed into tablets.

Pharmaceutical compositions of the invention adapted for oraladministration are a preferred embodiment of the invention. The diluentsand carriers used are preferably therefore those that adapt the activeingredient or ingredients for oral administration. Examples of suchdiluents and carriers are solid vehicles, excipients and lubricants suchas glucose, lactose and sucrose, corn and potato starch, sodiumcarboxymethylcellulose, ethyl cellulose and cellulose acetate, powderedgum tragacanth, gelatin, alginic acid, agar, talc, stearic acid andsodium, calcium and magnesium stearates, sodium lauryl sulphate,polyvinyl-pyrrolidone, sodium citrate, calcium carbonate, and dicalciumphosphate.

The pharmaceutical compositions of the invention may also contain othernon-toxic adjuvants and modifiers such as dyes, surfactants, perfumes,flavouring agents, such as sweeteners, preservatives and biocides.

Pharmaceutical compositions of the invention adapted for parenteralinjection are another preferred embodiment of the invention. Thediluents and carriers used are therefore preferably those that adapt theactive ingredient for parenteral administration. Examples of diluentsand carriers that adapt the active ingredient for parenteraladministration are solvents and suspending diluents such as water,vegetable fatty oils, such as sesame oil, groundnut oil, corn oil, andcottonseed oil, aqueous propylene glycol, N,N'-dimethylformamide, anddimethyl sulphoxide. In general, any non-aqueous diluent can be usedthat does not reduce the activity of the active ingredient and isnon-toxic in the dose employed.

For the administration of the water-soluble compounds of the inventionby parenteral injection sterile aqueous solutions can be employed, andare within the scope of the pharmaceutical compositions of theinvention. Such aqueous solutions should preferably when necessary bebuffered in the usual manner, and the liquid diluent should preferablybefore administration be rendered isotonic by adding the requisiteamount of salt or glucose. Such sterile buffered isotonic solutions areespecially suitable for intravenous, intramuscular and intraperitonealinjections. These pharmaceutical compositions of the invention canfurther contain local anaesthetics or substances that promote thediffusion of the active ingredient, for example hyaluronidase.

The pharmaceutical compositions of the invention preferably contain 0.5to 90 wt.% of at least one new compound of the invention.

The present invention also provides medicaments in dosage unit form ashereinafter defined comprising as an active ingredient at least onecompound of general formula (1) given above either along or in admixturewith a pharmaceutically acceptable solid or liquid diluent or carrier.In this case the diluent or carrier is preferably as defined above butcan also be water or another common solvent.

The expression "medicament in dosage unit form" as used in the presentspecification means a medicament in the form of discrete portions eachcontaining a unit dose or a multiple or sub-multiple of a unit dose ofthe active ingredients(s); for example, one, two, three or four unitdoses or a half, a third or a quarter of a unit dose. A "unit dose" isthe amount of the active ingredient(s) to be administered on oneoccasion and will usually be a daily dose, or for example a half, athird, or a quarter of a daily dose depending on whether the medicamentis to be administered once or, for example, twice, three times, or fourtimes a day.

The discrete portions constituting the medicament in dosage unit formcan include a protective envelope. The active ingredient can beundiluted and contained in such an envelope, or can be mixed with apharmaceutically acceptable solid or liquid diluent or carrier asdefined above. Such portions can for example be in monolithic coherentform, such as tablets, lozenges, pastilles, pills, suppositories, ordragees; in wrapped or concealed form, the active ingredients beingwithin a protective envelope, such as wrapped powders, cachets, sachets,capsules, or ampoules; or in the form of a sterile solution suitable forparenteral injection, such as ampoules of buffered, isotonic, sterile,pyrogen-free aqueous solution; or in any other form known in the art.

As stated above, peroral administration is a preferred mode ofadministration. Preferred medicaments in dosage unit form according tothe invention are therefore those adapted for oral administration, suchas tablets, pills, dragees, capsules, and cachets, as well as wrappedpowders containing the active ingredient in powdered form with apowdered diluent or carrier for suspension in water before being taken.

As also stated above a further preferred mode of administration isparenteral administration. Preferred medicaments in dosage unit formaccording to the invention are therefore those adapted for parenteralinjection, such as ampoules containing a measured quantity of a sterileisotonic saline injectable aqueous solution of the new activeingredient, which may be buffered with a pharmaceutically acceptablebuffer and are preferably free of pyrogens.

The preferred unit dose for administration of the medicaments of theinvention is 250 - 16000 mg. of active ingredient, preferably 1250 -4000 mg. This will usually be administered once daily.

The invention further provides a method of combatting bacterialinfection in an animal which comprises administering to the animal(preferably parenterally or perorally) an effective amount of one of thenew compounds, either alone, as a pharmaceutical composition accordingto the invention, or as a medicament in dosage unit form according tothe invention.

Indications envisaged in human medicine are especially generalinfections, and infections of the efferent urinary tract, caused byGram-positive and Gram-negative bacteria and by mycoplasma, and inveterinary medicine are general infections caused by Gram-negative andGram-positive bacteria and my mycoplasma. Infections of the respiratorypassages in poultry, especially in chicks, and mastitis of cows, may bementioned particularly

The new compounds can, as has already been mentioned, also be employedas a feedstuff additive, predominantly in raising young animals,especially chicks and fatstock.

The preparations can be administered in the feedstuff, special feedstuffpreparations and feedstuff concentrates, but also via the drinkingwater.

The invention therefore also provides animal feedstuffs and feedstuffconcentrates containing at least one of the new compounds of generalformula (1).

The administration of the new compounds together with the feedstuff orfeedstuff preparations and/or with the drinking water makes it possibleto prevent or treat infections by both Gram-negative and Gram-positivebacteria and mycoplasma, and can furthermore contribute to betterutilization of the feedstuff. As examples of frequently occurringveterinary illnesses which cause considerable economic damage and whichcan be prevented or treated by administering the new compounds in thefeedstuff or in the drinking water, there may be mentioned, in additionto general infections, infection of the air sac in chicks, and mastitisin cows.

What is claimed is:
 1. A veterinary feedstuff which comprises a growthpromoting amount of a compound of the formula ##SPC13##or apharmaceutically acceptable non-toxic salt thereof wherein Y ishydrogen, an alkali metal cation or the cation R⁵ --NH₃ ^(+;) and eachof R and R⁵ is identical to or different from the other and is##EQU1##in which R³ is alkyl of 1 to 4 carbon atoms or hydroxyalkyl of 1to 4 carbon atoms in combination with a nutritious material.
 2. Theveterinary feedstuff according to claim 1 wherein Y is hydrogen.
 3. Theveterinary feedstuff according to claim 1 wherein Y is a sodium orpotassium cation.
 4. The veterinary feedstuff according to claim 1 inoral administration form.
 5. The veterinary feedstuff according to claim1 in subcutaneous administration form.
 6. The veterinary feedstuffaccording to claim 1 wherein the compound is ##SPC14##or apharmaceutically acceptable non-toxic alkali metal or alkaline earthmetal salt thereof.
 7. The veterinary feedstuff according to claim 1wherein the compound is ##SPC15##
 8. The veterinary feedstuff accordingto claim 1 wherein the compound is ##SPC16##
 9. The veterinary feedstuffaccording to claim 1 wherein the compound is ##SPC17##
 10. Theveterinary feedstuff according to claim 1 wherein the compound is##SPC18##or a pharmaceutically acceptable non-toxic alkali metal oralkaline earth metal salt thereof.
 11. The veterinary feedstuffaccording to claim 1 wherein the compound is ##SPC19##or apharmaceutically acceptable non-toxic alkali metal or alkaline earthmetal salt thereof.
 12. A method of promoting growth in animals whichcomprises feeding an animal a growth promoting amount of the feedstuffof claim
 1. 13. The method according to claim 12 wherein Y is hydrogen.14. The method according to claim 12 wherein Y is a sodium or potassiumcation.
 15. The method according to claim 12 wherein the compound is##SPC20##or a pharmaceutically acceptable non-toxic alkali metal oralkaline earth
 16. The method according to claim 12 wherein the compoundis ##SPC21##
 17. The method according to claim 12 wherein the compoundis ##SPC22##
 18. The method according to claim 12 wherein the compoundis ##SPC23##
 19. The method according to claim 12 wherein the compoundis ##SPC24##or a pharmaceutically acceptable non-toxic alkali metal oralkaline earth
 20. The method according to claim 12 wherein the compoundis ##SPC25##or a pharmaceutically acceptable non-toxic alkali metal oralkaline earth metal salt thereof.